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Small (Weinheim An Der Bergstrasse,... Sep 2020Traditional liquid marbles (LMs), liquid droplets encapsulated by hydrophobic particles at the liquid-gas interface, are restricted by their short lifetime and low heat...
Traditional liquid marbles (LMs), liquid droplets encapsulated by hydrophobic particles at the liquid-gas interface, are restricted by their short lifetime and low heat transfer efficiency. Herein, a new paradigm for LMs immersed in various liquid mediums with massive enhanced heat transfer and spatial recognition is designed; without compromising the structural integrity, the lifetime of the liquid marbles in liquid (LMIL) is extended by ≈1000 times compared to classical LMs in air or naked droplets in organic reagents. The LMIL shows promising reverse structural re-configurability while under external stimuli and maintaining their functionality for a very long period of time (≈weeks). These superior behaviors are further exploited as a miniature reactor with prolonged lifetimes and excellent temperature control, combined with its feasible operation, new opportunities will open up in the advanced chemical and biomedical engineering fields. It is also shown that LMIL can be applied in methylene blue degradation and 3D in-vitro yeast cell cultures. These findings have important implications for real-world use of LMs, with a number of applications in cell culture technology, lab-in-a-drop, polymerization, encapsulation, formulation, and drug delivery.
Topics: Calcium Carbonate; Hydrophobic and Hydrophilic Interactions; Methylene Blue
PubMed: 32797713
DOI: 10.1002/smll.202002802 -
Toxicology Jun 2023The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of... (Review)
Review
The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of programmed cell death. Necroptosis is a necrotic and inflammatory type of programmed cell death. Phenothiazines are D1 and D2-like family receptor antagonists, which are used in the treatment of schizophrenia. Necroptosis begins from TNF-α, whose synthesis is stimulated by dopamine receptors, thus it can be concluded that phenothiazine derivatives may modulate necroptosis. We identified 19 papers reporting in vitro assays of necroptosis and necrosis in which phenothiazine derivatives, and both normal and cancer cell lines were used. Chlorpromazine, fluphenazine, levomepromazine, perphenazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate necroptosis and necrosis. The type of a drug, concentration and a cell line have an impact on the ultimate effect. Unfortunately, the authors confirmed both processes on the basis of TNF-α and ATP levels as well as the final steps of necrosis/necroptosis related to membrane permeability (PI staining, LDH release, and HMGB1 amount), which makes it impossible to understand the complete mechanism of phenothiazines impact on necroptosis and necrosis. Studies analyzing the effect of phenothiazines on RIPK1, RIPK3, or MLKL has not been performed yet. Only the analysis of the expression of those proteins as well as necrosis and necroptosis inhibitors can help us to comprehend how phenothiazine derivatives act, and how to improve their therapeutic potential.
Topics: Humans; Tumor Necrosis Factor-alpha; Necroptosis; Phenothiazines; Antipsychotic Agents; Necrosis
PubMed: 37127180
DOI: 10.1016/j.tox.2023.153528 -
Indian Journal of Pharmacology 2020
Topics: Cataract; Chlorpromazine; Diagnosis, Differential; Female; Humans; Middle Aged; Schizophrenia
PubMed: 33078739
DOI: 10.4103/ijp.IJP_691_20 -
Biochemistry. Biokhimiia Sep 2022Methylene blue (MB) is the first fully synthetic compound that had found its way into medicine over 120 years ago as a treatment against malaria. MB has been approved... (Review)
Review
Methylene blue (MB) is the first fully synthetic compound that had found its way into medicine over 120 years ago as a treatment against malaria. MB has been approved for the treatment of methemoglobinemia, but there are premises for its repurposing as a neuroprotective agent based on the efficacy of this compound demonstrated in the models of Alzheimer's, Parkinson's, and Huntington's diseases, traumatic brain injury, amyotrophic lateral sclerosis, depressive disorders, etc. However, the goal of this review was not so much to focus on the therapeutic effects of MB in the treatment of various neurodegeneration diseases, but to delve into the mechanisms of direct or indirect effect of this drug on the signaling pathways. MB can act as an alternative electron carrier in the mitochondrial respiratory chain in the case of dysfunctional electron transport chain. It also displays the anti-inflammatory and anti-apoptotic effects, inhibits monoamine oxidase (MAO) and nitric oxide synthase (NOS), activates signaling pathways involved in the mitochondrial pool renewal (mitochondrial biogenesis and autophagy), and prevents aggregation of misfolded proteins. Comprehensive understanding of all aspects of direct and indirect influence of MB, and not just some of its effects, can help in further research of this compound, including its clinical applications.
Topics: Methylene Blue; Mitochondria; Monoamine Oxidase; Neuroprotective Agents; Nitric Oxide Synthase
PubMed: 36180986
DOI: 10.1134/S0006297922090073 -
Contact Dermatitis Jul 2020In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter...
BACKGROUND
In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter (OTC) for the treatment of mosquito bites and pruritus in France.
OBJECTIVE
To report a series of cases with photodermatitis following use of topical phenothiazines.
METHOD
A retrospective study of cases of contact dermatitis from phenothiazines seen in French photodermatology centers was performed.
RESULTS
In all, 14 patients with a diagnosis of contact dermatitis from phenothiazines were included. These patients developed eczema on the application sites, and in 13 the eruption spread to photodistributed sites. Topical products containing isothipendyl were the most common cause of photodermatitis. One patient had photoaggravated eczema due to promethazine cream. All patients stopped using topical phenothiazines and were treated successfully with topical corticosteroids. One patient relapsed and developed persistent light eruption. In all of the nine cases tested, photopatch testing to the topical phenothiazine used "as is" was positive. Isothipendyl, chlorproethazine, and the excipients were not tested. Photopatch tests to chlorpromazine and promethazine were positive in 8 of 12 and 7 of 13 tested, respectively.
CONCLUSION
Use of isothipendyl and promethazine as OTC (or even prescribed) drugs needs to be limited due to severe reactions and sensitization to other phenothiazines that consequently will have to be avoided.
Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Chlorpromazine; Dermatitis, Photoallergic; Female; Histamine Antagonists; Humans; Male; Middle Aged; Phenothiazines; Promethazine; Thiazines
PubMed: 32124458
DOI: 10.1111/cod.13509 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2020Cyclic RGD peptides are well-known ligands of integrins. The integrins α β and α β are involved in angiogenesis, and integrin α β is abundantly present on cancer...
Cyclic RGD peptides are well-known ligands of integrins. The integrins α β and α β are involved in angiogenesis, and integrin α β is abundantly present on cancer cells, thus representing a therapeutic target. Hence, synthetic and biophysical studies continuously are being directed towards the understanding of ligand-integrin interaction. In this context, the development of versatile synthetic strategies to obtain fluorescent building blocks that can add molecular diversity and modular spectral characteristics while not compromising binding affinity or selectivity is a relevant task. An on-resin intramolecular Suzuki-Miyaura cross-coupling (SMC) between l- or d-7-bromotryptophan (7BrTrp) and a phenothiazine (Ptz) boronic acid affords fluorescent cyclic RGD pseudopeptides, c(RGD(W/w)Ptz). Ring closure by SMC establishes a phenothiazine-indole moiety with axial chirality. An array of eight novel compounds has been synthesized, among them one fluorescent compound with good affinity to integrin α β . The fluorescence properties of the analogues can be efficiently tuned depending on the substituents in Ptz moiety even for fluorescence emission in the visible (red) spectral range.
Topics: Fluorescence; Integrin alphaVbeta3; Ligands; Oligopeptides; Phenothiazines
PubMed: 32297686
DOI: 10.1002/chem.202001312 -
Journal of Applied Toxicology : JAT Apr 2023In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the... (Review)
Review
In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.
Topics: Animals; Antipsychotic Agents; Zebrafish; Promazine; Phenothiazines; Chlorpromazine; Mammals
PubMed: 36165981
DOI: 10.1002/jat.4397 -
European Journal of Medicinal Chemistry Jun 2023Cancer is a leading cause of death worldwide and there are still limited options for cure. Chemotherapy is the most significant treatment for cancer which increased... (Review)
Review
Cancer is a leading cause of death worldwide and there are still limited options for cure. Chemotherapy is the most significant treatment for cancer which increased survival rates, despite this, it is associated with numerous side effects, as well as cancer relapsing due to drug resistance insurgence; consequently, it is still a challenging task to develop new potent and less toxic anti-cancer agents for patients' care. Phenothiazine moiety, which leads a class of well-known antipsychotic drugs, possesses a wide range of biological activities and has been also introduced in cancer chemotherapy. This review aims in disclosing the use of phenothiazines during the last five years for the development of different anti-cancer drug candidates. The design and the synthetic strategies adopted, the SAR investigations and the role of reviewed phenothiazine derivatives as anti-cancer agents and multi-drug resistance (MDR) reversals are here fully described and discussed.
Topics: Humans; Phenothiazines; Antineoplastic Agents; Antipsychotic Agents; Drug Resistance, Multiple
PubMed: 37060756
DOI: 10.1016/j.ejmech.2023.115337 -
Journal of Applied Toxicology : JAT Jan 2021Drug repositioning is an approach that could accelerate the clinical use of compounds in different diseases. The goal is to take advantage of the fact that approved... (Review)
Review
Drug repositioning is an approach that could accelerate the clinical use of compounds in different diseases. The goal is to take advantage of the fact that approved drugs have been tested on humans and detailed information is available on their pharmacology, toxicity and formulation. It can significantly reduce the costs and time needed to implement necessary therapies on the market. In recent years, phenothiazines are being tested for cancer, viral, bacterial, fungal and other diseases. Most research focuses on chlorpromazine as a model drug in this class, but other drugs such as fluphenazine, perphenazine and prochlorperazine have been proven to inhibit the viability of different cancer cell lines. In this study, we performed an extensive literature search to find and summarize all papers on the chosen phenothiazines and their potential in treating different types of cancerin vitro for further animal/clinical trials. Fluphenazine, perphenazine and prochlorperazine possess anticancer activity towards different types of human cancer. The antitumor activity is mainly mediated by an effect of the drugs on the cell cycle, proliferation or apoptosis. Possible molecular targets of phenothiazine derivatives are the drug's efflux pumps (ABCB1 and P-glycoprotein) and two parallel pathways (AKT and Wnt) regulated by the D receptor antagonists. The drugs have the potential to reduce the viability of human cancer cell lines, fragment the DNA, stimulate apoptosis, inhibit cell migration and invasiveness as well as impair the production of reactive oxygen species. In addition, due to the sedative and antiemetic properties antipsychotics can be used as an adjuvant for the treatment of chemotherapy side effects.
Topics: Antineoplastic Agents; Antipsychotic Agents; Dopamine Antagonists; Drug Repositioning; Fluphenazine; Humans; In Vitro Techniques; Neoplasms; Perphenazine; Prochlorperazine
PubMed: 32852120
DOI: 10.1002/jat.4046 -
The Journal of the Association of... Apr 2022Many novel drugs were used in COVID19 pandemic to improve outcome. One such molecule is Methylene blue which is a, tricyclic phenothiazine compound approved for the... (Observational Study)
Observational Study
UNLABELLED
Many novel drugs were used in COVID19 pandemic to improve outcome. One such molecule is Methylene blue which is a, tricyclic phenothiazine compound approved for the treatment of acquired methemoglobinemia and some other uses US FDA. This molecule was found to inhibit the interaction of COVID19 virus and target cells in dose dependent manner. It was also found to inhibit interaction of viron with host cells, by inhibiting interaction of SARS CoV2 spike protein and ACE inhibitor receptor interactions.
MATERIAL AND METHODS
A) Aim & Objectives: To evaluate the effect of Nebulised Methylene blue on the clinical course and outcomes of patients with COVID-19 infections. B) Study design Observational Study C) Participants 63 COVID19 RT-PCR positive cases divided in 3 groups. Group 1 consists of patients who were prescribed Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with bronchodilator Levosalbutamol (1.25 mg) + Ipratropium (500 mcg) three times a day . Group 2 consists of patients with Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with inhalational steroid Budesonide (1 mg). Group 3 acted were those patients who had no Methylene blue nebulisation in their treatment.
OBSERVATION
1) Analysis 63 cases were divided in 3 groups of 21 each, descriptive and frequency analysis of cases in groups are shown.
CONCLUSION
No statistically significant difference in outcome measures like Spo2, duration of hospital stay or inflammatory markers. A general trend of fall in inflammatory markers and O2 requirements in group receiving methylene blue but this difference was not consistantly statistically significant.
Topics: Humans; Methemoglobinemia; Methylene Blue; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35443513
DOI: No ID Found